Comparison of Adaptive Neuroprotective Mechanisms of Sulforaphane and its Interconversion Product Erucin in in Vitro and in Vivo Models of Parkinson's Disease

J Agric Food Chem. 2018 Jan 31;66(4):856-865. doi: 10.1021/acs.jafc.7b04641. Epub 2018 Jan 22.

Abstract

Several studies suggest that an increase of glutathione (GSH) through activation of the transcriptional nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the dopaminergic neurons may be a promising neuroprotective strategy in Parkinson's disease (PD). Among Nrf2 activators, isothiocyanate sulforaphane (SFN), derived from precursor glucosinolate present in Brassica vegetables, has gained attention as a potential neuroprotective compound. Bioavailability studies also suggest the contribution of SFN metabolites, including erucin (ERN), to the neuroprotective effects of SFN. Therefore, we compared the in vitro neuroprotective effects of SFN and ERN at the same dose level (5 μM) and oxidative treatment with 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells. The pretreatment of SH-SY5Y cells with SFN recorded a higher (p < 0.05) active nuclear Nrf2 protein (12.0 ± 0.4 vs 8.0 ± 0.2 fold increase), mRNA Nrf2 (2.0 ± 0.3 vs 1.4 ± 0.1 fold increase), total GSH (384.0 ± 9.0 vs 256.0 ± 8.0 μM) levels, and resistance to neuronal apoptosis elicited by 6-OHDA compared to ERN. By contrast, the simultaneous treatment of SH-SY5Y cells with either SFN or ERN and 6-OHDA recorded similar neuroprotective effects with both the isothiocyanates (Nrf2 protein 2.2 ± 0.2 vs 2.1 ± 0.1 and mRNA Nrf2 2.1 ± 0.3 vs 1.9 ± 0.2 fold increase; total GSH 384.0 ± 4.8 vs 352.0 ± 6.4 μM). Finally, in vitro finding was confirmed in a 6-OHDA-PD mouse model. The metabolic oxidation of ERN to SFN could account for their similar neuroprotective effects in vivo, raising the possibility of using vegetables containing a precursor of ERN for systemic antioxidant benefits in a similar manner to SFN.

Keywords: 6-hydroxydopamine; Nrf2; Parkinson’s disease; erucin; sulforaphane.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brassica / chemistry
  • Cell Line, Tumor
  • Dopaminergic Neurons / chemistry
  • Dopaminergic Neurons / drug effects*
  • Glutathione / analysis
  • Humans
  • Isothiocyanates / metabolism
  • Isothiocyanates / pharmacology*
  • Isothiocyanates / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / analysis
  • NF-E2-Related Factor 2 / genetics
  • Neuroblastoma
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidation-Reduction
  • Oxidopamine / administration & dosage
  • Parkinson Disease / prevention & control*
  • RNA, Messenger / analysis
  • Sulfides / metabolism
  • Sulfides / pharmacology*
  • Sulfides / therapeutic use
  • Thiocyanates / metabolism
  • Thiocyanates / pharmacology*
  • Thiocyanates / therapeutic use

Substances

  • Isothiocyanates
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Neuroprotective Agents
  • RNA, Messenger
  • Sulfides
  • Thiocyanates
  • Oxidopamine
  • erucin
  • sulforaphane
  • Glutathione